1. Field of Invention
The present invention is concerned with the use of aryl and aryloxyalkyl compounds which carry one or more sulfamate radicals as anticonvulsants useful in the treatment of convulsions in mammals.
2. Information Disclosure Statement
Esterification of glycols having the formula HOCH.sub.2 (CRR').sub.n CH.sub.2 OH wherein R,R'=H, alkyl, or aryl; n=0-8; with R.sup.2 R.sup.3 NSO.sub.2 Cl wherein R.sup.2, R.sup.3 =H, alkyl, aryl or R.sup.2 R.sup.3 N=pyrrolidinyl, or piperidinyl; to give (R.sup.2 R.sup.3 NSO.sub.2 OCH.sub.2).sub.2 (CRR').sub.n which compounds are useful as contraceptives and have been disclosed in Ger. Offen. 2,559,210 (C.A. 85, 142662w). While the compounds do fall within the scope of those useful in the methods of this invention, the utility is different. Formula I compounds of the present invention do not fall within the scope of this earlier disclosure.
U.S. Pat. No. 4,513,006 discloses anticonvulsant and carbonic anhydrase inhibiting properties of sulfamate esters of the formula: ##STR1## where X=O or CH.sub.2, R.sup.1 is hydrogen or lower alkyl, and R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are hydrogen, loweralkyl and when X is CH.sub.2, R.sup.4 and R.sup.5 may form a benzene ring and when X is O, R.sup.2 and R.sup.3 and/or R.sup.4 and R.sup.5 together may form a methylenedioxy group of the formula: ##STR2## where R.sup.6 and R.sup.7 are hydrogen, loweralky, or R.sup.6 and R.sup.7 together form a cyclopentyl or cyclohexyl ring.
Sulfamates of 2,3,4,5-bis-O-(1-methylethylidene)-.beta.-D-fructopyranose and related compounds such as 2,2-dimethyl-1,3-dioxolan-4-yl)methyl sulfamate and compounds of the formula Ph-CHRCH.sub.2 OSO.sub.2 NH.sub.2 are disclosed in U.S. Pat. No. 4,591,601 and J. Med. Chem. (1987) 30, pp. 880-887 as having anticonvulsant activity. Certain of the compounds of the present invention having the formula ArO(CR'R.sup.2).sub.m OSO.sub.2 NH.sub.2 appear to be somewhat similar but are novel.
Compounds having the formula ##STR3## wherein R.sup.3 and R.sup.4 are hydrogen or loweralkyl and R.sup.2 is methyl, ethyl, alkyl, etc. are disclosed in Ger. Offen. 2,417,764 (C.A. 84, 30709q) as herbicides.
Erucyl sulfamate and oleyl sulfamate are disclosed in U.S. Pat. No. 3,661,830 as slip additives for polyethylene. In contrast, in a preferred novel method of this invention, alcohols are treated with sulfamic acid phenyl ester in boiling p-dioxane with a non-nucleophilic organic base to prepare compounds of Formula I.
2-Hydroxyaryl sulfamate esters having the formula 2--OH--C.sub.6 H.sub.4 --OSO.sub.2 NHCH.sub.2 Ph are disclosed in J. Org. Chem. (1980) 45(26), 5373-5 (C.A. 94, 15312t) as intermediates in the preparation of sulfamides.
Some of the compounds of this invention are included in a co-pending U.S. application, Ser. No. 365,212 filed June 12, 1989, which discloses the novelty and utility of these compounds in treating chronic arthritis and osteoporosis and a process for preparing the compounds. Additional novel compounds are disclosed in the present invention.